Minor histocompatibility antigens (minor HA) appear to play an important role in the pahtogenesis of graft-versus-host disease (GVHD) in human recipients of bone marrow transplants from HLA and MLC matched donors. I have developed a murine model of minor HA-GVHD in two strain combinations selected for H-2 identity and for mutual nonreactivity in MLC: C57BL/6-LP (H-2b combination) and B10.D2/NSN-BALB/c (H-2d) combination. This model possesses many characteristics in common with human GVHD, including acute and chronic forms. I will utilize this model to systematically study the immune mechanisms which produce GVHD in response to minor HA. The inducer T-cells, which must be included in the marrow innoculum for GVHD to develop, will be characterized. The repertoire of effector mechanisms of GVHD, including both cell mediated and humoral immune responses, will be studied in vitro and in vivo and the specific cellular targets of GVHD will be identified. Cogenic strains of mice developed between C57BL/10, LP and 129 mice will be used to identify which specific minor HA function as targets of GVHD. The information obtained from these studies will provide the basis for future studies of the immunoregulation of the immune responses which result in GVHD.